The aim of the proposed project is to compare the neurochemical mechanisms underlying ethanol and barbiturate tolerance and dependence in an effort to achieve a more generalized conceptualization of the development of CNS tolerance and dependence on sedative hypnotics. Evidence from acute studies with barbiturates, and from our previous studies with ethanol, suggest that catecholaminergic and cholinergic systems, as well as interactions between these systems and with other neurotransmitter systems, may be crucial in development and/or expression of tolerance and dependence. Animal models for chronic consumption of ethanol and barbiturates will be used which allow monitoring, by physiologic and behavioral means, the development of tolerance and dependence, and the correlation of changes in neurotransmitter metabolism or function with these phenomena. Neurotransmitter turnover, enzyme activities associated with neuronal activity, the interactions of agonists with their neuronal receptors will be assessed during chronic treatment with sedative hypnotics and during withdrawal.